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Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer

ABSTRACT: Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer

PROVIDER: PRJNA512271 | ENA |

REPOSITORIES: ENA

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Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer

Project description:Despite cisplatin-based neoadjuvant chemotherapy (NAC) 60% of patients with muscle-invasive bladder cancer still have residual invasive disease at radical cystectomy (RC). The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. We analyzed gene expression from 133 patients with residual invasive disease after cisplatin-based NAC. H&E and immunohistochemistry were used to confirm tissue sampling and gene expression analysis. Established molecular subtyping models proved to be inconsistent in their classification of the post-NAC samples. Unsupervised consensus clustering revealed four distinct consensus clusters (CC). The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal-like and a luminal-like phenotype, respectively. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecule expression, but lacked both basal and luminal markers. The CC4-Scar-like subtype expressed genes associated with wound-healing/ scarring and was associated with favorable prognosis.

2019-01-01 | GSE124305 | GEO

Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival outcome to neoadjuvant chemotherapy: results from a multi-institutional validation study

Project description:Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).

2017-05-25 | GSE87304 | GEO

Differential neoadjuvant chemotherapy response in urothelial carcinoma molecular subtypes

Project description:For patients with muscle-invasive bladder cancer, there are no biomarkers in clinical use that can identify patients that are sensitive or resistant to neoadjuvant chemotherapy. This study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cis-platin based chemotherapy by tumor classification using transcriptomic profiling and a 13-marker immunostaining panel. Furthermore, we explored to what extent gene expression signatures can predict chemotherapy response beyond molecular subtypes. We observed improved pathological response rates and survival outcomes for patients presenting with genomically unstable (GU) and urothelial-like (Uro) subtypes compared to the basal-squamous (BASQ) subtype following neoadjuvant chemotherapy and radical cystectomy. Also, SPP1, coding for osteopontin, displayed a clear subtype-dependent effect on chemotherapy response, confirmed at the protein level. Based on our findings, we hypothesize that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy which may influence patient selection pending further research.

2021-11-19 | GSE169455 | GEO

Genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer

Project description:This SuperSeries is composed of the following subset Series: GSE25055: Discovery cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer GSE25065: Validation cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer Refer to individual Series

2011-05-11 | E-GEOD-25066 | biostudies-arrayexpress

Association of Molecular Subtypes with Pathologic Response, PFS and OS in a Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy (NAC) for Localized, Muscle-Invasive Bladder Cancer (SWOG S1314; NCT02177695)

Project description:Investigation of RNA-based molecular subtypes as additional predictive biomarkers for neoadjuvant chemotherapy response, progression-free survival and survival in patients treated in S1314.

2023-11-28 | GSE244266 | GEO

Response to Neoadjuvant Chemotherapy in Triple Negative Breast tumors.

Project description:In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched. Whole genome expression of triple negative breast cancer tissues were measured before and after four cycles neoadjuvant chemotherapy

2016-03-24 | E-GEOD-43816 | biostudies-arrayexpress

Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients

Project description:Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor-specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease-free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.

2014-06-17 | MTBLS92 | MetaboLights

Radiation induced gene signature predicts pathologic complete response to neoadjuvant chemotherapy in breast cancer patients

Project description:Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response. reference x sample

2015-01-21 | E-GEOD-48073 | biostudies-arrayexpress

Improved T cell immunity following neoadjuvant chemotherapy in ovarian cancer

Project description:To investigate effects of standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy on T cell immunity, we surveyed changes in the peripheral T cell receptor repertoire. We performed bulk TCR sequencing of peripheral blood before chemotherapy (baseline), after 3 cycles (C3) and after 6 cycles (C6).

2022-06-22 | GSE206339 | GEO

Acquired semi-squamalization during chemotherapy suggests a differentiation therapy for bladder cancer

Project description:Cisplatin-based chemotherapy is the most common treatment for unresectable bladder cancers and also increasingly used as neoadjuvant treatments before or after surgery and radiotherapy. Unfortunately, though many patients respond to the treatment, most of them develop resistance quickly with unclear mechanisms and few further treatment options. Here, we report that semi-squamazation is acquired during chemo treatment in both mice and human. Multi-omics analyses show that cathepsin H (CTSH), a direct target of p63, is associated with chemoresistance and semi-squamation. Treatment with the cathepsin inhibitor E64 specifically restrains chemoresistant but not chemosensitive cancer. Mechanistically, cathepsin inhibition induces fully squamous differentiation of bladder cancer cells, which requires TNF receptor 1alpha and is associated with pyroptosis. Our study suggests that semi-squamazation would be a diagnosistic marker for chemoresistance and differentiation therapy by targeting CTSH might be a potential treatment for chemoresistant bladder cancer.

2022-07-09 | GSE192575 | GEO

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